Alavi, A

ABSTRACTBackgroundThere is a known association between common variable immunodeficiency (CVID) and granulomas in multiple organ systems, including the skin, lung, liver, and spleen. Rubella virus has also been detected within cutaneous granulomas in both immunocompetent and immunocompromised hosts. We present a retrospective case series of patients with CVID and granulomatous skin disease and describe the spectrum of clinical and histopathologic features, including the status of rubella virus in the cutaneous granulomas.MethodsWe retrospectively reviewed the clinical and histopathological characteristics of patients diagnosed with CVID at our institution, with cutaneous findings and skin biopsies available for review between 1990 and 2023, demonstrating granulomatous inflammation.ResultsEight patients met the inclusion criteria. The most common histopathologic pattern was palisaded granulomatous inflammation, seen in five of eight cases. Three cases showed strictly sarcoidal granulomas. Background inflammation was peri‐granulomatous (8/8) and the predominant background inflammatory cell type was lymphocytic (6/8). Rubella virus testing was performed for seven of eight cases and found to be positive in one case.ConclusionCutaneous granulomatous disease in CVID can present with a spectrum of clinical morphologies, granulomatous patterns, and variable rubella virus persistence. Dermatopathologists should be aware of the spectrum of findings when considering cutaneous CVID–related granulomatous disease in the differential diagnosis.

AbstractIntroductionThe International Hidradenitis Suppurativa Severity Score System (IHS4) is a validated tool that measures inflammatory lesions, including draining tunnels, in hidradenitis suppurativa (HS).ObjectiveTo evaluate secukinumab efficacy using IHS4 in patients with moderate to severe HS.MethodsData from the SUNSHINE and SUNRISE trials, which assessed subcutaneous secukinumab 300 mg every 2 (SECQ2W) and 4 (SECQ4W) weeks in adults with moderate to severe HS, were analyzed. Assessments included changes from baseline in IHS4 and severity classification up to Week 52; IHS4‐55, IHS4‐75, IHS4‐90 responses (55%, 75% and 90% reduction in IHS4) and concordance between IHS4‐55 and HS clinical response (HiSCR), at Weeks 16 and 52.ResultsIn total, 1084 patients (SECQ2W = 361; SECQ4W = 360; placebo = 363) were analyzed. At Week 16, SECQ2W and SECQ4W demonstrated a numerically higher reduction in IHS4 from baseline versus placebo (adjusted mean [95% CI]: −10.80 [−12.30 to −9.30] and −9.46 [−10.96 to −7.96] vs. −4.92 [−6.43 to −3.41]); the reduction was maintained until Week 52 in both dose regimens. A greater proportion of patients achieved IHS4‐55 with SECQ2W (43.4%) and SECQ4W (39.5%) versus placebo (31.5%) at Week 16, with further improvement at Week 52. Similar trends were observed for IHS4‐75 and IHS4‐90 responses. While no patients had mild disease based on IHS4 (80.7% had severe and 19.3% had moderate HS) at baseline, a greater proportion of patients were categorized as having mild disease at Week 16 in the SECQ2W (25.9%) and SECQ4W (24.0%) groups versus placebo (16.4%); this trend continued up to Week 52 in both dose regimens. Strong concordance (>85%) was observed between IHS4‐55 and HiSCR.ConclusionsBoth SECQ2W and SECQ4W demonstrated efficacy in improving treatment response as measured by IHS4 and reducing disease severity versus placebo at Week 16 and these improvements were sustained through Week 52. These findings support that the dynamic and dichotomous IHS4 can efficiently detect treatment response changes in clinical trial settings.Clinical Trials RegistrationSUNSHINE (NCT03713619); SUNRISE (NCT03713632).

Abstract Background Perianal draining tunnels in hidradenitis suppurativa (HS) and perianal fistulizing inflammatory bowel disease (IBD) present diagnostic and management dilemmas. Methods We conducted a retrospective chart review of patients with perianal disease evaluated at Mayo Clinic from January 1, 1998, through July 31, 2021. Patients' demographic and clinical data were extracted, and 28 clinical features were collected. After experimenting with several machine learning techniques, random forests were used to select the 15 most important clinical features to construct the diagnostic prediction model to distinguish perianal HS from fistulizing perianal IBD. Results A total of 263 patients were included (98 with HS, 100 with IBD, and 65 with both IBD and HS). Patients with HS had a higher mean body mass index, a higher smoking rate, and more commonly showed cutaneous manifestations of tunnels and comedones, while fistulas, abscesses, induration, anal tags, ulcers, and anal fissures were more common in patients with IBD. In addition to having lesions in the perianal area, patients with IBD often had lesions in the buttocks and perineum, while those with HS had additional lesions in the axillae and groin. Among the statistically significant features, the 15 most important were identified by random forest: fistula , tunnel , digestive symptom , knife‐cut ulcer , perineum , body mass index , age , axilla , abscess , tags , smoking , groin , genital cutaneous edema , erythema , and bilateral/unilateral . Conclusions The results of this study may help differentiate perianal lesions, especially perineal HS and fistulizing perineal IBD, and provide promise for a better therapeutic outcome.

Abstract Background Immune checkpoint inhibitors (ICIs) have transformed cancer treatment by targeting immune checkpoints such as PD‐1, PDL‐1, and CTLA‐4, but concerns about severe immune‐related adverse events persist. The scarcity of literature on dermatologic implications, especially severe reactions such as Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), highlights the urgent need for investigation. Objective Our systematic review aims to address the gap in relevant literature by extensively examining the epidemiologic risk factors and management of SJS/TEN‐like illnesses in ICI‐treated patients to provide insights for risk assessment and clinical care. Method s We identified 158 case reports that detailed the incidence of SJS/TEN in patients being treated with ICIs, examining demographic patterns, type of malignancy, clinical characteristics, and treatments linked to onset. We assessed mortality rates, risk elements, and the effectiveness of interventions to help guide clinical care. Results Analysis of 158 case reports revealed that SJS/TEN in ICI users is typically seen on average at the age of 63 and is more common in males. PD1 inhibitors such as nivolumab and pembrolizumab are often associated with various mucocutaneous patterns and significant risks with ICI use, especially TEN, which is linked to high morbidity and mortality rates. Limitations Our study notes limitations due to the inclusion of case reports or case series, such as potential publication and reporting biases, leading to skewed findings. Additionally, because of the heterogeneous reporting standards, the retrospective nature limits phenotypic precision, control for confounding variables, and data completeness. Conclusion Our study provides valuable insights into the epidemiology, clinical features, management strategies, and outcomes of ICI‐induced SJS/TEN, underscoring the importance of vigilant monitoring and personalized risk assessment in oncology practice. Continued research efforts are essential to optimize patient outcomes and enhance the safety profile of ICIs in cancer therapy.

AbstractPregnancy is a conjectured risk factor for pyoderma gangrenosum (PG), an autoinflammatory neutrophilic dermatosis characterized by painful ulcers. Even so, there are no available treatment guidelines for those with PG who are pregnant or breastfeeding. To describe existing treatment options, we systematically reviewed the literature on PG treatment in pregnant or breastfeeding patients. A search over four databases was completed in October 2022. Independent reviewers accomplished screening and data extraction. 18 articles met the inclusion criteria. 15 cases involved the treatment of PG during pregnancy, and three cases involved the treatment of PG while breastfeeding. Most patients did not have a history of PG prior to pregnancy (77.7%), and most did not have PG‐associated comorbidity (61.1%). Of the cases involving treatment of PG during pregnancy, the majority (73%) found treatment success with a systemic corticosteroid (SCS). Only three cases reported an adverse outcome, including premature rupture of membranes and premature birth (16.7%); all these cases involved treatment with a SCS at >0.5 mg/kg/day during pregnancy. We present a treatment algorithm for pregnant or breastfeeding patients with PG. Our findings suggest prioritizing topicals and TNF inhibitors due to more favorable side effect profiles. However, there is a paucity of data on the safety of PG therapies in pregnancy and breastfeeding, and thus, controlled studies and pregnancy registries must be pursued.

AbstractBackgroundThe hidradenitis suppurativa (HS) clinical response (HiSCR) has come under scrutiny as several HS clinical trials failed to meet primary endpoints with high placebo responses. This may be due to limitations of the tool and raters' ability to accurately characterize and count lesions, rather than lack of efficacy of the studied drug. Due to HS lesion complexity and potential differences in rater training, it was hypothesized that there would be discrepancies in how providers characterize and count lesions for HS clinical trials.ObjectiveTo evaluate how HS providers and patients name and count HS lesions and to identify discrepancies among providers to initiate the development of consensus‐driven guidance for HS rater training.MethodsAn online survey was distributed to the members of HIdradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC). Respondents were asked to classify lesion images composed of multiple and different morphology types and answer questions regarding inclusion of associated dermatological conditions.ResultsForty‐seven HISTORIC members responded (29 providers; 18 patients). There was variability in how respondents classified HS lesions. Of 12 questions containing images, four had ≥50% of respondents choosing the same answer. With an image of a lesion composed of different morphologies, 45% of providers counted it as a single lesion and 45% counted it as multiple distinct lesions. With an image of multiple interconnected draining tunnels, 7% of providers classified it as a single draining tunnel while 79% categorized it as multiple draining tunnels with the number estimated by visual inspection. There was also variability in deciding whether lesions occurring in associated conditions should be considered separately or included in HS lesion counts. Patient responses were also variable.ConclusionsThe result of the current study reaffirms the gap in how providers characterize and count HS lesions for clinical trials and the need to develop consensus‐driven rater training related to HS outcome measures.

AbstractWe report a case of a 41‐year‐old woman who developed pregnancy‐associated pyoderma gangrenosum (PG) at 4 weeks gestation. She was initially treated with prednisone, however, due to lack of improvement and risk of systemic corticosteroids in pregnancy, underwent a prednisone taper and was initiated on certolizumab pegol (CZP). The patient experienced complete wound re‐epithelialization 1 month after CZP initiation. She had no pregnancy complications except for prednisone‐associated gestational diabetes and gave birth to a healthy baby. CZP is a tumour necrosis factor‐inhibitor with negligible placental transfer and no known adverse effects in pregnancy. Its efficacy and safety for autoinflammatory dermatoses in pregnancy are very promising. This is the first case to report CZP treatment for PG in a pregnant patient.

AbstractBackgroundDermatology grand rounds are popular educational activities among dermatologists and trainees, contributing to improved knowledge and skills. Dermatology hospital conferences at Mayo Clinic Dermatology are separate from dermatology grand rounds in that they focus on inpatient consultations and dermatology admissions.ObjectivesThis study aimed to determine the types of cases presented during dermatology hospital grand rounds and evaluate the educational value of this continuing medical education (CME)‐accredited activity.MethodsThis retrospective study reviewed all inpatient dermatology cases presented during hospital grand rounds at Mayo Clinic Dermatology in Rochester, MN from 2019 to 2022; this study also reviewed the compiled surveys of faculty participants at our institution from 2019 to 2022.ResultsA total of 389 cases met the inclusion criteria for analysis. The most common diagnostic category was inflammatory/autoimmune diseases (157 cases, 40%), followed by infection or infestation (73 cases, 19%), drug‐induced eruptions (49 cases, 13%), neoplastic or metastatic diseases (41 cases, 11%), genetic/congenital disorders (21 cases, 5%), depositional/nutritional/metabolic conditions (15 cases, 4%) and wound/traumatic/iatrogenic dermatoses (12 cases, 3%), which were the least common. Most cases were presented for discussion of diagnosis and management (246 cases, 63%), but others focused on the arrival of diagnosis (119 cases, 31%) or management alone (24 cases, 6%). The compiled surveys of faculty participants (n = 50) indicated high satisfaction with dermatology hospital grand rounds, with the majority expressing that evidence‐based research was incorporated and positively impacted their practice. Most respondents indicated that hospital conference participation improved knowledge (97%), competence (64%), clinician performance (54%), patient outcomes (52%) and team performance (50%).ConclusionsThe cases presented during these conferences spanned from challenging inflammatory diseases to simple dermatoses, with over 800 literature references reviewed. Dermatology hospital grand rounds provide high value as a CME‐accredited activity for dermatology faculty, even for those without a specific interest in hospital/inpatient dermatology.

AbstractBackgroundHidradenitis suppurativa (HS) is a chronic inflammatory skin condition that causes substantial physical, emotional and psychological burdens. Guselkumab, a monoclonal antibody that binds to the p19 subunit of interleukin‐23, has demonstrated high levels of efficacy in the treatment of inflammatory diseases, including psoriasis and psoriatic arthritis.ObjectiveTo evaluate the effect of guselkumab on the treatment of HS, a phase 2, multicentre, randomized, placebo‐controlled, double‐blind, proof‐of‐concept study was conducted.MethodsPatients ≥18 years of age with moderate‐to‐severe HS for ≥1 year were randomized to (1) guselkumab 200 mg by subcutaneous (SC) injection every 4 weeks (q4w) through Week 36 (guselkumab SC); (2) guselkumab 1200 mg intravenously (IV) q4w for 12 weeks, then switched to guselkumab 200 mg SC q4w from Weeks 12 through 36 (guselkumab IV); or (3) placebo for 12 weeks, with re‐randomization to guselkumab 200 mg SC q4w at Weeks 16 through 36 (placebo → guselkumab 200 mg) or guselkumab 100 mg SC at Weeks 16, 20, 28 and 36 and placebo at Weeks 24 and 32 (placebo → guselkumab 100 mg). End points included HS clinical response (HiSCR) and patient‐reported outcomes.ResultsAlthough guselkumab SC or guselkumab IV resulted in numerically higher HiSCR versus placebo at Week 16 (50.8%, 45.0%, 38.7%, respectively), statistical significance was not achieved. Numerically greater improvements in patient‐reported outcomes were also observed for guselkumab SC and guselkumab IV versus placebo at Week 16. Through Week 40, no clear differences to suggest a dose response were observed for HiSCR and patient‐reported outcomes.ConclusionsDespite modest improvements, the primary end point was not met and the overall findings do not support the efficacy of guselkumab in the treatment of HS. Clinicaltrials.gov: NCT 03628924.